We are continuing to develop the synthesis of protected peptide fragments on solid supports using amino acid esters of oximes as the anchoring groups. We have found that peptides can be assembled on oxime-containing polymeric supports under conditions similar to those customarily employed in solid-phase synthesis by the usual Merrifield stepwise approach and that protected peptide fragments can be removed from the polymer by mild treatment with hydrazine. Subsequently, it should be possible to convert the hydrazides to azides for further coupling of the fragments. At present, most of our efforts are devoted to determining which of the oxime-containing polymers we have prepared is best for the fragment synthesis. Development of the polymer-bound oxime ester method should enable us to synthesize peptides containing up to 50-60 amino acids by a combination of fragment synthesis and condensation. Since this approach should aid the preparation of polypeptides having single amino acid replacements in crucial regions, synthetic studies of structure-activity relationships for a variety of rather large biologically important peptides should be facilitated. We are already engaged in studies on the synthesis of a truncated model of pancreatic trypsin inhibitor (Kunitz) and the neurotoxin sea anemone toxin III. In our further work we expect to submit a variety of oxime derivatives to the National Cancer Institute's anti-tumor Screening Program.